PROJECT SUMMARY/ABSTRACT Rates of obesity in the United States have doubled over the last 30 years, as has the percentage of persons in the U.S. with diagnosed Type 2 diabetes (T2D), and both conditions are rapidly increasing worldwide. Although changes in diet and energy expenditure have played an important role, insufficient sleep and circadian misalignment have been identified as novel risk factors for the development of such metabolic diseases and are often unavoidable in modern, 24-hour society (e.g. long work hours, jet lag, medical residency, emergency responders, military personnel, shift workers). Humans spend up to one third of their lives asleep and yet the function of sleep remains a topic of intense debate. While evidence supports a role for sleep in learning, memory and other central nervous system functions, clinical studies have demonstrated that sleep restriction has adverse effects on metabolism, both at the whole body, as well as molecular level. Over the last century, the average sleep duration in American adults has decreased by nearly 2 hours per night. Insufficient sleep impairs insulin sensitivity, resulting in insulin resistance?the biggest risk factor for the development of diabetes?yet our mechanistic understanding underlying this risk remains unknown, especially with respect to tissue-specific metabolic alterations. Previous studies and our preliminary data resulting from research supported by the current K01 suggest that sleep loss may impact adipose and skeletal muscle tissue insulin sensitivity and function, however, in depth assessments of peripheral metabolic tissues in the context of insufficient sleep have not been conducted. We expect that achievement of these aims will yield the following expected outcomes. First, these results will establish that insufficient sleep leads to adverse effects directly at the adipose and skeletal tissue and will reveal that sleep plays an integral role in the regulation of adipose and skeletal tissue insulin sensitivity. Second, these data will generate mechanisms by which sleep loss induces insulin resistance in peripheral metabolic tissues. Third, the proposed project will provide Dr. Broussard additional molecular-based training in adipose and skeletal muscle biology that will further distinguish her from her K01 mentors. Completion of the proposed project will generate critical preliminary data that will allow Dr. Broussard pursue a future independent scientific career at the intersection of metabolism and sleep/circadian biology. These outcomes will have an important and immediate impact as they will reveal insufficient sleep causes tissue-specific insulin resistance, which could be targeted to prevent and treat metabolic diseases. The contribution of the proposed research is expected to be identification of alterations in both adipose and muscle tissue following sleep loss in humans. This contribution will be significant because direct assessments of adipose and muscle tissue in the context of insufficient sleep will reveal new therapeutic targets and/or countermeasures to combat the growing incidence insulin resistance and diabetes.